CN102247618B - Dermal filler composition - Google Patents
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- CN102247618B CN102247618B CN201110095861.9A CN201110095861A CN102247618B CN 102247618 B CN102247618 B CN 102247618B CN 201110095861 A CN201110095861 A CN 201110095861A CN 102247618 B CN102247618 B CN 102247618B
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Abstract
The present invention relates to a novel dermal filler composition and to a method for preparing same. The composition of the present invention comprises, as a main component, cross-linked dextran, the molecular weight of which is 30,000 to 100,000. The composition can rapidly augment a defective area of the skin and maintain softness to the touch even when used alone. The composition eliminates the necessity of a pretreatment, such as an allergy test, which might otherwise be required prior to injection, is inexpensive, and is not easily decomposed or absorbed in vivo, thereby maintaining the tissue-volume augmentation effects thereof over a long period of time after injection. Therefore, the composition is suitable for use in a procedure such as penile augmentation or the like which requires the injection of a large amount of dermal filler, i.e. more than 20 cc. The composition of the present invention can be prepared through a simplified process to make the composition easily usable. The composition is soft to the touch when injected under the skin, and can thus be applicable not only to the skin of the penis but also to the skin of other parts of the human body, Including the face.
Description
Technical field
The present invention relates to a kind of new dermal filler composition of any form and preparation method thereof of just can giving rapidly in being injected into body.
Background technology
The soft tissue (soft tissue) of human body maintains its structure by the protein such as collagen, elastin and the extracellular matrix that comprises mucopolysaccharide, in the time of disappearance due to reason generation soft tissues such as congenital reason or external impact or the causes of disease, restore or correct its form by insert bio-tissue or synthetic macromolecular compound expansion soft tissue at its corresponding site.To be injected into specific part by injection with the similar composition of skin histology and expand soft tissue, thereby generally be called dermal filler (dermal filler) or filler (filler) for the material that improves wrinkle or correction profile etc.And such dermal filler is divided into following two types according to the mechanism of action of its display effect: a class dermal filler is that the direct extended volume of material by injecting shows expansion effect; Another kind of dermal filler also forms the new autologous tissue as collagen by the stimulation of material at periphery and shows volume effect except injected material shows direct volume effect.
In addition, can also be divided into following three types according to the timeliness of dermal filler.
The first, in 1 year, decompose rapidly and absorbed dermal filler; The second, the length of decomposing that the time limit decomposes rapidly with in described 1 year and absorbed dermal filler is compared, but finally can decompose also absorbed dermal filler; Three, can not decompose in vivo the dermal filler of permanent delay.
Belong to direct extended volume as collagen (collagen) or the hyaluronic acid (hyaluronic acid) etc. of the main component of at present conventional dermal filler and show expansion effect, in 1 year, decompose rapidly and absorbed dermal filler; The one-tenth such as polyacrylamide (polyacrylamide) belong to direct extended volume and do not decompose in vivo the dermal filler of permanent delay; Polymethyl methacrylate (PMMA) belongs to except the direct volume effect of injected material the also stimulation by material and forms the new autologous tissue as collagen at periphery and show volume effect, do not decompose in vivo the permanent dermal filler being detained; Cross-linking dextran belongs to except the direct volume effect of injected material the also stimulation by material and forms the new autologous tissue as collagen at periphery and show volume effect, the length of decomposing that the time limit decomposes rapidly with in described 1 year and absorbed dermal filler is compared, but finally can decompose also absorbed dermal filler.
Preferred dermal filler need to possess following condition: the first, the outstanding and safety of biocompatibility; The second, because the cheap burden in the use of expense is few; Three, the volume effect of transplantation site can continue more than 2 years for a long time.
At present conventional dermal filler separately taking collagen or hyaluronic acid (hyaluronic acid) as the product of main component in the majority.First, the dermal filler using collagen as main component has: main component is that the EVOLENCE 30 (trade (brand) name of ColBar Life Technologies Corporation dermal filler) of pig collagen (porcine collagen), Zyderm that main component is bovine collagen (bovine collagen) or the Zyplast trade (brand) name of Inamed company dermal filler (above for), main component are the CosmoDerm of human collagen (human collagen) or the CosmoPlast trade (brand) name of Inamed company dermal filler (above for) etc.Using hyaluronic acid (hyaluronicacid) having as main component: Rofilan (trade (brand) name of Rofil/Philoderm company dermal filler), Perlane, Restylane (being the trade (brand) name of Medicis/Q-Med AB company dermal filler above), Teosyal (trade (brand) name of Teoxane SA company dermal filler), Surgiderm (trade (brand) name of Corneal Laboratoire company dermal filler) etc.But, the only dermal filler using collagen or hyaluronic acid (hyaluronic acid) as main component, for its expensive price the persistent period of effect too short, so practical application is clinically restricted.
In addition the product that, timeliness is grown has: MATRIDEX and CRMDx (trade (brand) name of BioPolymer GmbH & Co.KG company dermal filler) using hyaluronic acid (hyaluronic acid) and cross-linking dextran (DEAE sephadex) as main component.When dermal filler main component is hyaluronic acid (hyaluronic acid) and cross-linking dextran particle, when injection, show immediately that volume expands effect, hyaluronic acid (hyaluronic acid) decomposed and was absorbed through 6 to 12 months, and its space is by being subject to cross-linking dextran to stimulate the autologous collagen newly forming to fill.Hyaluronic acid (hyaluronic acid) is for utilizing the intercellular substance composition between epidermis and corium to make cell be bonded with each other, play the material of intercellular lubricating oil effect, and the hyaluronic acid (hyaluronic acid) that injection is used with dermal filler is synthetic.From timeliness aspect, hyaluronic acid (hyaluronic acid) disappears final decomposition in 1 year, all decompose and disappear although cross-linking dextran is final after the long period of lasting 1 year to 2 years, due to the formation of the autologous tissues such as the collagen newly forming, its effect is comparatively lasting.But because hyaluronic acid (hyaluronic acid) composition has accounted for the major part of product, there is the problem that dermal filler is quite expensive.
Than described in comprise cross-linking dextran the more lasting product of dermal filler effect have the Artefill (trade (brand) name of ArtesMedical company dermal filler) using polymethyl methacrylate (PMMA) and collagen as main component.First, after becoming liquid condition, mixes with polymethyl methacrylate (PMMA) the collagen composition (bovine collagen) of refining cattle, then be injected into corium and maintain volume expansion effect to get off, in the case of applying such dermal filler, polymethyl methacrylate (PMMA) shows immediately and expands effect after injection, self the collagen that is absorbed by the decomposition of collagen that the space that produces newly forms by the stimulation of polymethyl methacrylate (PMMA) is filled, thereby maintains volume expansion effect.But due to the extract that the collagen using is cattle, come from animal, so must carry out the pre-treatments such as anaphylactogen skin test (allergic skin test) before using, this causes large obstacle to practical clinical.In addition, because collagen composition is quite expensive, therefore exist the financial burden of patient while executing art large, the collagen composition that accounts for most of small product size decomposes too rapidly absorption (all absorbing in 3 to 6 weeks) and cannot guarantee the shortcoming maintaining owing to forming virgin rubber original volume in the time injecting in human body.In addition, polymethyl methacrylate (PMMA) composition can not decompose at leisure in vivo but be detained, and is therefore difficult to eliminate the fear to there is in the future the probability of side effect, and this is also a reason that hinders its use.
In addition, the compositions for systemic recovery or expansion using polymethyl methacrylate (PMMA) as basic polymer, dextran etc. as carrier is disclosed in the people's such as Boume US Patent No. 2003/0233150.But, as mentioned above, in described US Patent No. 2003/0233150, can not decompose at leisure in vivo due to polymethyl methacrylate (PMMA) composition but is detained, therefore there is the probability of generation side effect.In addition, the in the situation that of application cross-linking dextran (cross-linked dextran), be injected into rear portion in tissue and directly expand volume, simultaneously can be by macrophage phagocytic, in a period of time, cause in vivo that foreign body reaction carrys out the formation of inducing self-body collagen and then plays expansion effect, after the dextran (dextran) using in the people's such as Bourne described US Patent No. 2003/0233150 by contrast exists and is injected in organism, in a few days, decomposing and bring into play volume expansion effect, is only the problem of simple carrier (carrier).
Recently, occurred the dermal filler composition (No. 10-0759091st, patent) taking polymethyl methacrylate (PMMA) and cross-linking dextran (cross-linked dextran) as main component, it has improved the problem of a part of above-mentioned existing dermal filler.
Said composition is being executed the preoperative pre-treatments such as anaphylactogen skin test that do not need, and expense is cheap, and be not easy to decompose in vivo absorb and effect is lasting, therefore need to inject a large amount of dermal fillers more than 20cc injection penis expand operation also can use.After but described compositions is injected into below skin, its sense of touch is harder, thus expand applicable to injection penis, but be not suitable for needing other a lot of positions of human body of comparatively soft sense of touch to use in face etc.
In addition, use two kinds of main polymers owing to mixing, make complicated process of preparation and be difficult to obtain the license that human body uses, therefore have practical more difficult problem.
In addition,, because polymethyl methacrylate (PMMA) composition can not decompose but the cause of being detained in vivo at leisure, be still difficult to eliminate the fear to there is in the future the probability of side effect.
In addition, in dermal filler, there is not the dermal filler as main component by cross-linking dextran separately, its reason is that the molecular weight of the cross-linking dextran of attached use in existing all dermal fillers is 30, (ProductName: DEAE Sephadex 25) below 000, the droplet size (bead size) of drying regime is 40 μ m to 120 μ m, in 0.15M sodium-chloride water solution when aquation, the diameter of droplet size (bead size) intermediate value is 127 μ m, the diameter of hydrated state/drying regime is 1.83 (being converted to volume ratio is 6.1) than only, make volume expand effect very small, and the words that there is no carrier (carrier) are difficult to inject, must must there be collagen or hyaluronic acid (hyaluronic acid) etc. oneself to there is the carrier (carrier) of volume effect, and the sense of touch of injecting position can feel very hard due to the hard capsule of tissue reaction's formation.(with reference to Fig. 2), therefore, existing cross-linking dextran injects difficulty and injects position and produces hard sense of touch while there is use separately, and the single main component of uncomfortable cooperation filler must be added the problem that the materials such as collagen or hyaluronic acid use as the double main component of carrier (carrier).
Summary of the invention
(1) technical problem that will solve
The present invention is for solving the problem of the dermal filler that above-mentioned prior art uses, even be 30 by molecular weight in the present invention, 000 to 100,000 cross-linking dextran is also easy to inject as the independent use of main component of dermal filler, and can maintain the soft sense of touch of injecting position.
In addition, the object of the present invention is to provide a kind of dermal filler composition, they are different from the existing dermal filler institute using collagen or hyaluronic acid (hyaluronic acid) as main component, it does not comprise collagen or hyaluronic acid, therefore execute the preoperative pre-treatments such as anaphylactogen skin test that do not need, and the expense of dextran is cheap, more be difficult in vivo decompose absorption than collagen or hyaluronic acid, make the volume expansion effect of executing art maintain stablely more for a long time than collagen or hyaluronic acid, thereby be also applicable to need in the operation such as injection penis expansion of a large amount of dermal fillers more than 20cc, and due to from existing using different as the dermal filler of main component to polymethyl methacrylate (PMMA) and cross-linking dextran, it does not comprise polymethyl methacrylate (PMMA), thereby eliminate and can slowly not decompose because of composition but be detained the fear of the side effect producing in vivo, therefore be easy to permit human body to use, and preparation technology is comparatively simply easy to practical.In addition, sense of touch is soft when being injected into below skin, not only can be used for skin of penis, and all can use on the skin at other a lot of positions of human body such as face.
(2) technical scheme
For realizing described object, the invention provides a kind of new dermal filler composition that just can give rapidly any form and maintain soft sense of touch in being injected into body, more specifically, provide a kind of molecular weight 30,000 to 100,000, the dermal filler composition that comprises cross-linking dextran, sodium-chloride water solution and viscosity modifier (except the situation that comprises polymethyl methacrylate (PMMA)).
In addition, the invention provides a kind of dermal filler composition, the described dermal filler composition of every 10ml comprises: 0.3～0.4g molecular weight is 30, process cytotoxicity in 000 to 100,000 is removed the cross-linking dextran of processing, the sodium-chloride water solution as isotonic solution and the viscosity modifier (except the situation that comprises polymethyl methacrylate (PMMA)) of pH6～pH8.Described viscosity modifier uses 0.02～0.06g while being hydroxypropyl emthylcellulose (HPMC).
In addition, the invention provides a kind of dermal filler composition, the described dermal filler composition of every 10ml comprises: 0.3～0.4g molecular weight is 30, cross-linking dextran in 000 to 100,000, the sodium-chloride water solution as isotonic solution of pH6～pH8 and viscosity modifier (except the situation that comprises polymethyl methacrylate (PMMA)).Described viscosity modifier uses 0.02～0.06g while being hydroxypropyl emthylcellulose (HPMC).The invention still further relates to the preparation method of dermal filler composition, object is to provide a kind of preparation method of dermal filler composition, described method comprises: be 30 at 0.3～0.4g molecular weight, in cross-linking dextran in 000 to 100,000, put into lasting cleaning of normal saline (0.9% sodium-chloride water solution) solution of dextran space outerpace is adjusted to isotonic solution; The pH of the sodium-chloride water solution that is adjusted to isotonic solution is adjusted to pH6～pH8; Add viscosity modifier.Now, consider in cross-linking dextran and may have impurity, preferably carry out cytotoxicity and remove processing.When comprising cytotoxicity and removing treatment step, the preparation method of dermal filler composition comprises: in distilled water, put into 0.3～0.4g molecular weight 30,000 to 100,000 cross-linking dextran carries out aquation, and under certain hour, high temperature, high pressure, carry out after sterilization treatment, remove the distilled water that is not absorbed into cross-linking dextran hydras inside, then add sodium-chloride water solution to make the toxin stripping of cross-linking dextran inside; In cytotoxicity is removed the cross-linking dextran of processing, put into normal saline (0.9% sodium-chloride water solution) toward described, and continue to clean and make the solution of described cross-linking dextran space outerpace be adjusted to isotonic solution; The pH of the solution of the described dextran space outerpace that is adjusted to isotonic solution is adjusted to pH6～pH8; Add viscosity modifier.
(3) beneficial effect
The present invention is not by being that the polymer substance extracting from animal forms, and therefore production technology is simple, and does not use the collagen of high price, has significantly reduced preparation cost.
The present invention uses molecular weight 30,000 to 100, in 000, remove the cross-linking dextran of processing as the main component of dermal filler through cytotoxicity, for the new departure not proposed in existing dermal filler, have and be easy to inject dermal filler, injection unit potential energy enough maintains the effect of more soft sense of touch.
In addition, from existing using different as the dermal filler of main component to collagen or hyaluronic acid (hyaluronic acid), it does not comprise collagen or hyaluronic acid, make Shi Shushi not need to carry out the pre-treatments such as anaphylactogen skin test, and the expense of dextran is cheap, also be not easy in vivo to decompose and absorb, it is stable more for a long time that the volume that makes to execute art expands effect, thereby the operation such as injection penis expansion that is also adapted at injecting the above a large amount of dermal fillers of 20cc is used.
Particularly, from using different as the dermal filler of main component with two kinds of cross-linking dextrans (crosslinked dextran) polymethyl methacrylate (PMMA), it is not included in and injects the permanent polymethyl methacrylate being detained in position, having eliminated the melancholy of the probability to having side effects in the future considers, make the human body usage license easier, preparation technology is simpler, thereby be easier to practical, and there is soft sense of touch when being injected into below skin, not only at the skin of penis, and can use on the skin at other a lot of positions of human body such as face.
Brief description of the drawings
Fig. 1 is the bottle schematic diagram that dermal filler of the present invention is housed.
Fig. 2 is to be 30 by the molecular weight of attached use in current all dermal filler compositions, the cross-linking dextran of (ProductName: DEAE Sephadex25) below 000 and the molecular weight of dermal filler composition of the present invention are 30, cross-linking dextran in 000 to 100,000 is with identical content bottle schematic diagram when aquation in normal saline (0.9% sodium-chloride water solution).
Detailed description of the invention
Therefore, the cross-linking dextran of existing dermal filler composition is in the time being injected in body by injection, because pin hole the phenomenon such as is blocked and is difficult to inject, and it is small that the volume that injects position expands effect, and there is very hard sense of touch, therefore for being easy to, existing dermal filler composition carries out injecting in body, and while injection, there is immediately volume and expand effect and soft sense of touch, and must add collagen or hyaluronic acid etc. and have carrier (carrier) use afterwards of volume effect.But, as the present invention by molecular weight 30,000 to 100,000 cross-linking dextran is during as the main component of dermal filler, have not mix and use collagen or hyaluronic acid and only use cross-linking dextran as main component and be also easy to injection and inject, it is very outstanding that volume expands effect, injects the advantage of the soft-touch at position.In addition, the present invention is owing to not comprising collagen or hyaluronic acid, therefore do not need to execute the preoperative pre-treatments such as anaphylactogen skin test of carrying out, expense is cheap, and absorb owing to being difficult in vivo decomposing, expand effect and can more for a long time stably maintain volume, thereby the operation such as injection penis expansion that is also adapted at injecting a large amount of dermal fillers more than 20cc is used.
In addition, consider in the preparation process of cross-linking dextran in dermal filler composition of the present invention and may contain impurity, preferably also comprise that cytotoxicity removes treatment step.Cytotoxicity is removed treatment step by putting into 0.3～0.4g molecular weight 30 in distilled water, 000 to 100,000 cross-linking dextran carries out aquation, and under certain hour, high temperature, high pressure, carry out after sterilization treatment, remove the distilled water that is not absorbed into cross-linking dextran hydras inside, then add sodium-chloride water solution that the process of the toxin stripping of cross-linking dextran inside is realized.Now, for the volume that makes dextran particle can more effectively dwindle, preferably use the sodium-chloride water solution of more than 0.9% high concentration.
Dermal filler composition of the present invention as above is due to only using the cross-linking dextran of removing processing through cytotoxicity as main component, have harmless, preparation technology simple, be easier to practical, sense of touch is tender while being injected into below skin, thereby not only on the skin at other a lot of positions of human body such as skin of penis Shang Haike face, also can use go out chromatic effect.
The cross-linking dextran of molecular weight in 30,000 to 100,000 in the present invention preferably uses 0.3～0.4g in every 10mi dermal filler composition.Residual moisture while using 0.3g following
As the molecular weight of the main composition composition of dermal filler composition of the present invention 30,000 to 100,000 cross-linking dextran, for the droplet size (bead size) of drying regime is the small protoplast of 40 μ m to 120 μ m, in it is injected into tissue time, play immediately volume expansion effect, can do not engulfed by macrophage, the foreign body reaction that produces in vivo certain hour carrys out inducing self-body collagen and forms, thereby can continue to maintain volume amplification effect simultaneously.
In existing dermal filler, there is not the dermal filler of independent use cross-linking dextran as main component, its reason is that the molecular weight of the cross-linking dextran of attached use in existing all dermal fillers is 30, (ProductName: DEAE Sephadex 25) below 000, the droplet size (bead size) and of the present invention 30 of drying regime, 000 to 100, the droplet size (bead size) of 000 cross-linking dextran is identical, but in 0.15M sodium-chloride water solution when aquation, the diameter of droplet size (bead size) intermediate value is 127 μ m, the diameter of hydrated state/drying regime is than being only 1.83 (while being converted to volume ratio 6.1), make volume expand effect very small, and the words that there is no carrier (carrier) are difficult to inject, must must there is hyaluronic acid (hyaluronic acid) etc. oneself to there is the carrier (carrier) of volume effect, and inject the sense of touch at position because the hard pod membrane that tissue reaction forms can feel very hard.On the contrary, molecular weight of the present invention is 30,000 to 100,000 cross-linking dextran, in 0.15M sodium-chloride water solution when aquation, the diameter of droplet size (bead size) intermediate value is 214 μ m, the diameter ratio of hydrated state/drying regime is 3.17 (while being converted to volume ratio 31.8), it is very outstanding that volume expands effect, and be only himself to be just easy to injection inject, and do not need the carrier such as collagen or hyaluronic acid (hyaluronic acid), and inject the soft-touch at position.
Be described in detail by accompanying drawing, Fig. 1 is the bottle photo that dermal filler of the present invention is housed, Fig. 2 is to be 30 by the molecular weight of attached use in current all dermal filler compositions, the cross-linking dextran of (ProductName: DEAE Sephadex25) below 000 and the molecular weight of dermal filler composition of the present invention are 30, 000 to 100, 000 cross-linking dextran is with identical content bottle photo when aquation in normal saline (0.9% sodium-chloride water solution), compared with the cross-linking dextran using in existing dermal filler composition, can confirm that molecular weight of the present invention is 30, 000 to 100, it is very outstanding that the volume of 000 cross-linking dextran expands effect.Too much, make the cross-linking dextran of the amount identical with the amount of residual moisture be easy in vivo absorb, thereby exist the volume of executing art to expand the shortcoming that effect more can not for a long time stably maintain.While using 0.4g above, dermal filler injects position meeting hardening, sense of touch may be bad, therefore expand effect in order for a long time stably to maintain volume, make to inject position and maintain soft sense of touch, in every 10ml dermal filler composition, use 0.3～0.4g molecular weight at 30,000 to 100,000 cross-linking dextran.
In addition, for making dermal filler be suitable for being injected in body, in the present invention, sodium-chloride water solution is preferably the isotonic solution of pH6～pH8.
In addition, medium viscosity regulator of the present invention plays and makes the injection of dermal filler become the effect of being easy to by making cross-linking dextran maintain gel (gel) state.
Viscosity modifier has hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose (sodiumcarboxymethylcellulose), chitosan (chitosan), Polyethylene Glycol (polyethyleneglycol, PEG), poly lactic-co-glycolic acid amide (polylactic glycolamide, PLGA), polyvinyl alcohol (polyvinyl alcohol, PVA), dextran (dextran), hyaluronic acid (hyaluranic acid) or cross-linked-hyaluronic acid etc., can select one of them to use.
In described viscosity modifier, hydroxypropyl emthylcellulose (HPMC) the preferably content in every 10ml dermal filler composition is 0.02～0.06g.
In addition, the present invention relates to the preparation method of dermal filler composition, described method comprises: be 30 at 0.3～0.4g molecular weight, in 000 to 100,000 cross-linking dextran, put into normal saline (0.9% sodium-chloride water solution) and continue to clean the solution furnishing isotonic solution that makes dextran space outerpace; The pH of the sodium-chloride water solution that is adjusted to isotonic solution is adjusted to pH6～pH8; Add viscosity modifier.Now, consider in cross-linking dextran and may have impurity, preferably carry out cytotoxicity and remove processing.When comprising cytotoxicity and removing treatment step, dermal filler composition is prepared by following steps: in distilled water, putting into 0.3～0.4g molecular weight is 30,000 to 100,000 cross-linking dextran carries out aquation, and under certain hour, high temperature, high pressure, carry out after sterilization treatment, remove the distilled water that is not absorbed into cross-linking dextran hydras inside, then add sodium-chloride water solution to make the toxin stripping of cross-linking dextran inside; Put into normal saline (0.9% sodium-chloride water solution) toward the described cross-linking dextran of removing processing through cytotoxicity, and continue to clean and make the solution of described cross-linking dextran space outerpace be adjusted to isotonic solution; The pH of the solution of the described dextran space outerpace that is adjusted to isotonic solution is adjusted to pH6～pH8; Add viscosity modifier.
The cytotoxicity of described cross-linking dextran is removed treatment step, first in distilled water, put into 0.3～0.4g molecular weight and carry out aquation at 30,000 to 100,000 cross-linking dextran, make cross-linking dextran absorb water expand very large after, under certain hour, high temperature, high pressure, carry out sterilization treatment.
Afterwards, remove the distilled water that is not absorbed into cross-linking dextran hydras inside, add again sodium-chloride water solution, make the moisture of cross-linking dextran inside particles because osmotic pressure is discharged in the sodium-chloride water solution of dextran particle outside, make the volume-diminished of dextran particle, in this process, the toxin of cross-linking dextran inside also can be followed stripping, thus the toxicity of removing.Now, for more effectively dwindling the volume of dextran particle, preferably use the sodium-chloride water solution of 0.9% above high concentration.
In addition, the step that sodium-chloride water solution between cross-linking dextran hydras particle is adjusted to isotonic solution is: described in remove the sodium-chloride water solution between the cross-linking dextran particle obtaining in the Cytotoxic treatment step of cross-linking dextran, by osmotic pressure, the moisture of cross-linking dextran inside particles is discharged in the sodium-chloride water solution of dextran particle outside, the concentration of the sodium-chloride water solution unit volume sodium between cross-linking dextran particle is reduced (if or used more than 0.9% high concentration chlorination sodium water solution in the described Cytotoxic treatment step of removing cross-linking dextran time, by osmotic pressure, the moisture of cross-linking dextran inside particles is discharged in the sodium-chloride water solution of dextran particle outside, even if the solution of cross-linking dextran space outerpace is diluted to some extent, but its na concn still can be high compared with isotonic solution), for making described sodium-chloride water solution become isotonic solution, use normal saline (0.9% sodium-chloride water solution) to clean constantly, make solution and the sodium-chloride water solution of described cross-linking dextran space outerpace become isotonic solution.
In addition, the cross-linking dextran hydras that mixes up pH described in the step of described interpolation viscosity modifier makes maintains gel (gel) state, and the injection that makes dermal filler becomes easy, when this viscosity modifier is hydroxypropyl emthylcellulose, in the dermal filler that mixes up pH described in every 10mi, preferably add 0.02～0.06g.
Using cross-linking dextran cheap dermal filler composition of the present invention etc. when the dermal filler of main component is used, dermal filler can be injected into rapidly below corium by injection, make to maintain and be suitable for the rapid expansion at position and soft sense of touch simultaneously, different from existing dermal filler, it does not comprise collagen or hyaluronic acid, make to execute the preoperative pre-treatments such as anaphylactogen skin test that do not need, expense is cheap, be not easy in vivo decompose and absorb, make it possible to more for a long time stably maintain volume and expand effect, thereby being also suitable for expanding operation at the injection penis that need to inject more than 20cc a large amount of dermal fillers waits operation to use.
Especially, from using different as the dermal filler of main component with two kinds of cross-linking dextrans (crosslinked dextran) polymethyl methacrylate (PMMA), be not included in and inject the polymethyl methacrylate (PMMA) that position is for good and all detained, eliminate considering in the melancholy that side effect probability occurs in the future, make human body admission process easier, and because preparation technology more simply has and is easier to practical effect, and there is soft sense of touch when being injected into below skin, thereby have not only on skin of penis, and the outstanding effect that also can use on the skin at other extensive positions of human body such as face.
Claims (4)
1. a dermal filler composition, is characterized in that, composed of the following components:
Molecular weight is at 30,000 to 100,000 cross-linking dextran;
Sodium-chloride water solution; And
Viscosity modifier.
2. a dermal filler composition, is characterized in that, composed of the following components:
Cross-linking dextran, it is by putting into molecular weight 30 at distilled water, 000 to 100,000 cross-linking dextran carries out aquation, under certain hour, high temperature, high pressure, carry out after sterilization treatment, remove the distilled water that is not absorbed into cross-linking dextran hydras inside, then put into sodium-chloride water solution and make the toxin stripping of cross-linking dextran inside, thereby remove Cytotoxic processing procedure and obtain;
Sodium-chloride water solution; And
Viscosity modifier, it does not comprise polymethyl methacrylate.
3. dermal filler composition as claimed in claim 1 or 2, is characterized in that, the isotonic solution that sodium-chloride water solution is pH6～pH8.
4. a dermal filler composition, is characterized in that, every 10ml dermal filler composition is composed of the following components:
0.3～0.4g molecular weight is at 30,000 to 100,000 cross-linking dextran;
The sodium-chloride water solution isotonic solution of pH6～pH8; And
The hydroxypropyl emthylcellulose viscosity modifier of 0.02～0.06g.
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| KR10-2010-0043753 | 2010-05-11 | ||
| KR1020100043753A KR101003331B1 (en) | 2010-05-11 | 2010-05-11 | Dermal filler composition |
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| CN102247618A CN102247618A (en) | 2011-11-23 |
| CN102247618B true CN102247618B (en) | 2014-06-18 |
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| CN201110095861.9A Active CN102247618B (en) | 2010-05-11 | 2011-04-14 | Dermal filler composition |
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| US (1) | US9242030B2 (en) |
| EP (1) | EP2570141B1 (en) |
| JP (1) | JP2013524927A (en) |
| KR (1) | KR101003331B1 (en) |
| CN (1) | CN102247618B (en) |
| AU (1) | AU2011251138B2 (en) |
| BR (1) | BR112012028232B1 (en) |
| CA (1) | CA2794017C (en) |
| HK (1) | HK1163562A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2018203714A1 (en) * | 2017-03-09 | 2018-09-27 | Colin Campbell Marshall Moore | Improved Phalloplasty Method |
| AU2017101856B4 (en) * | 2017-05-02 | 2021-08-05 | Oates & Family Pty Ltd | Procedure for Penile Girth Enhancement |
| CN108653817B (en) * | 2018-05-24 | 2021-02-02 | 上海其胜生物制剂有限公司 | Preparation method of novel collagen stimulant |
| CN111558085A (en) * | 2020-06-16 | 2020-08-21 | 红色未来科技(北京)有限公司 | Face filler and preparation method thereof |
| KR102430642B1 (en) * | 2020-07-03 | 2022-08-16 | 주식회사 메피온 | Dermal filler composition and method for manufacturing thr same |
| CN113041397A (en) * | 2021-04-08 | 2021-06-29 | 红色未来科技(北京)有限公司 | A facial filler containing crosslinked dextran and its preparation method |
| CN113244450A (en) * | 2021-05-31 | 2021-08-13 | 美卓(杭州)医疗科技有限公司 | Active filler for resisting hand aging and preparation method thereof |
| CN114225117A (en) * | 2021-11-08 | 2022-03-25 | 红色未来科技(北京)有限公司 | A comprehensive facial filler containing crosslinked dextran and its preparation method |
| CN114146221A (en) * | 2021-12-09 | 2022-03-08 | 杭州帕莱拉医疗科技有限公司 | Injectable dextran hydrogel microsphere filling agent and preparation method thereof |
| CN115252896A (en) * | 2022-08-11 | 2022-11-01 | 成都恒美盛生物科技有限公司 | Material mixing method for producing facial filler |
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| CN101426451A (en) * | 2006-12-13 | 2009-05-06 | 曹康善 | Dermal filler composition |
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| US5502042A (en) * | 1994-07-22 | 1996-03-26 | United States Surgical Corporation | Methods and compositions for treating wounds |
| FR2764514B1 (en) | 1997-06-13 | 1999-09-03 | Biopharmex Holding Sa | IMPLANT INJECTED IN SUBCUTANEOUS OR INTRADERMAL WITH CONTROLLED BIORESORBABILITY FOR REPAIR OR PLASTIC SURGERY AND AESTHETIC DERMATOLOGY |
| US6060461A (en) * | 1999-02-08 | 2000-05-09 | Drake; James Franklin | Topically applied clotting material |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1678277A (en) * | 2002-07-29 | 2005-10-05 | 艾克里麦德公司 | Methods and compositions for treatment of dermal conditions |
| CN101426451A (en) * | 2006-12-13 | 2009-05-06 | 曹康善 | Dermal filler composition |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2794017A1 (en) | 2011-11-17 |
| RU2012146876A (en) | 2014-06-20 |
| AU2011251138A1 (en) | 2012-10-11 |
| EP2570141B1 (en) | 2018-07-25 |
| WO2011142530A3 (en) | 2012-01-05 |
| HK1163562A1 (en) | 2012-09-14 |
| WO2011142530A2 (en) | 2011-11-17 |
| US20130053453A1 (en) | 2013-02-28 |
| BR112012028232B1 (en) | 2018-09-04 |
| JP2013524927A (en) | 2013-06-20 |
| EP2570141A4 (en) | 2014-08-06 |
| KR101003331B1 (en) | 2010-12-23 |
| AU2011251138B2 (en) | 2013-11-14 |
| EP2570141A2 (en) | 2013-03-20 |
| CA2794017C (en) | 2014-11-18 |
| CN102247618A (en) | 2011-11-23 |
| US9242030B2 (en) | 2016-01-26 |
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